Μελέτη των φαινοτυπικών αλλαγών κυττάρων του νεφρικού παρεγχύματος κατά την ανάπτυξη της νεφρικής ίνωσης

Η Χρόνια Νεφρική Νόσος, το τελικό αποτέλεσμα των περισσότερων νεφρικών και ορισμένων συστηματικών παθήσεων, είναι μια κατάσταση στην οποία υπάρχει έκπτωση της νεφρικής λειτουργίας οφειλόμενη κυρίως στην ίνωση. Κατά την ανάπτυξη της νεφρικής ίνωσης, η calreticulin, μια πολυλειτουργική πρωτεΐνη-συνοδός του ενδοπλασματικού δικτύου υπερεκφράζεται στα σωληναριακά επιθηλιακά κύτταρα του νεφρού τόσο in vitro όσο και in vivo. Η πρωτεωμική ανάλυση σε κυτταρική σειρά σωληναριακών επιθηλιακών κυττάρων που υπερεκφράζουν calreticulin οδήγησε στην ταυτοποίηση της οικογένειας των 14-3-3 πρωτεϊνών. Η έκφραση της πλειοψηφίας των μελών της οικογένειας αυτής βρέθηκε αυξημένη σε τρία διαφορετικά ζωικά πρότυπα νεφρικών παθήσεων: το μοντέλο της μονόπλευρης ουρητηρικής απόφραξης, το μοντέλο της χορήγησης νεφροτοξικού ορού και το μοντέλο της ισχαιμίας-επαναιμάτωσης. Σε όλα τα μοντέλα, η ισομορφή 14-3-3σ (γνωστή και ως stratifin) είχε την μεγαλύτερη υπερέκφραση. Καθώς σε όλα τα μοντέλα που μελετήθηκαν η υποξία είναι κοινός παρανομαστής δείξαμε ότι ο επαγόμενος από την υποξία μεταγραφικός παράγοντας HIF1α προσδένεται στον υποκινητή του γονιδίου 14-3-3σ in vivo. Τέλος, αξιολογήσαμε την έκφραση της οικογένειας των 14-3-3 πρωτεϊνών καθώς και της ισομορφης 14-3-3σ σε βιοψίες από ασθενείς με σπειραματονεφριτιδες ποικίλης αιτιολογίας. Τα αποτελέσματα αυτά υποδεικνύουν εμπλοκή της 14-3-3σ στην νεφρική παθολογία και παρέχουν για πρώτη φορά στοιχεία ότι η υποξία μπορεί να είναι υπεύθυνη για την αλλαγή στην έκφρασή της.Chronic Kidney Disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised mainly due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is upregulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in three different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischemia-reperfusion. In all these models, the 14-3-3σ isoform (also known as stratifin) was predominantly overexpressed. Since in all these models ischemia is a common denominator, we showed that the ischemia-induced transcription factor HIF1α is specifically associated with the promoter region of the 14-3-3σ gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3σ in biopsies from patients with glomerulopathies of various etiology. These results establish an involvement of 14-3-3σ in renal pathology and provide evidence for the first time, that hypoxia may be responsible for its altered expression

Study of phenotypic changes of renal parenchymal cells during the development of renal fibrosis

Chronic Kidney Disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised mainly due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is upregulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in three different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischemia-reperfusion. In all these models, the 14-3-3σ isoform (also known as stratifin) was predominantly overexpressed. Since in all these models ischemia is a common denominator, we showed that the ischemia-induced transcription factor HIF1α is specifically associated with the promoter region of the 14-3-3σ gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3σ in biopsies from patients with glomerulopathies of various etiology. These results establish an involvement of 14-3-3σ in renal pathology and provide evidence for the first time, that hypoxia may be responsible for its altered expression.Η Χρόνια Νεφρική Νόσος, το τελικό αποτέλεσμα των περισσότερων νεφρικών και ορισμένων συστηματικών παθήσεων, είναι μια κατάσταση στην οποία υπάρχει έκπτωση της νεφρικής λειτουργίας οφειλόμενη κυρίως στην ίνωση. Κατά την ανάπτυξη της νεφρικής ίνωσης, η calreticulin, μια πολυλειτουργική πρωτεΐνη-συνοδός του ενδοπλασματικού δικτύου υπερεκφράζεται στα σωληναριακά επιθηλιακά κύτταρα του νεφρού τόσο in vitro όσο και in vivo. Η πρωτεωμική ανάλυση σε κυτταρική σειρά σωληναριακών επιθηλιακών κυττάρων που υπερεκφράζουν calreticulin οδήγησε στην ταυτοποίηση της οικογένειας των 14-3-3 πρωτεϊνών. Η έκφραση της πλειοψηφίας των μελών της οικογένειας αυτής βρέθηκε αυξημένη σε τρία διαφορετικά ζωικά πρότυπα νεφρικών παθήσεων: το μοντέλο της μονόπλευρης ουρητηρικής απόφραξης, το μοντέλο της χορήγησης νεφροτοξικού ορού και το μοντέλο της ισχαιμίας-επαναιμάτωσης. Σε όλα τα μοντέλα, η ισομορφή 14-3-3σ (γνωστή και ως stratifin) είχε την μεγαλύτερη υπερέκφραση. Καθώς σε όλα τα μοντέλα που μελετήθηκαν η υποξία είναι κοινός παρανομαστής δείξαμε ότι ο επαγόμενος από την υποξία μεταγραφικός παράγοντας HIF1α προσδένεται στον υποκινητή του γονιδίου 14-3-3σ in vivo. Τέλος, αξιολογήσαμε την έκφραση της οικογένειας των 14-3-3 πρωτεϊνών καθώς και της ισομορφης 14-3-3σ σε βιοψίες από ασθενείς με σπειραματονεφριτιδες ποικίλης αιτιολογίας. Τα αποτελέσματα αυτά υποδεικνύουν εμπλοκή της 14-3-3σ στην νεφρική παθολογία και παρέχουν για πρώτη φορά στοιχεία ότι η υποξία μπορεί να είναι υπεύθυνη για την αλλαγή στην έκφρασή της

Food Ingredients and Active Compounds against the Coronavirus Disease (COVID-19) Pandemic: A Comprehensive Review

As media reports have noted, the COVID-19 pandemic has accelerated market mainstreaming of immune-boosting food bioactives, supplements, and nutraceuticals. However, most studies reporting on the potential of bioactives against COVID-19 transmission have been uploaded as preprints with little opportunity to revise content for benefit and impact. The current review discusses current best evidence and information underpinning the role of food ingredients and bioactive compounds in supporting immune functions in humans and animals, specifically in the prevention and treatment of COVID-19 disease. Up to now, some evidence from randomized population and clinical trials has suggested that vitamin D levels may be linked to COVID-19 transmission and severity. Numerous theoretical studies have pointed to polyphenols and particularly flavonoids as potential inhibitors of SARS-CoV-2 infection. There is also inconclusive evidence to support the future use of β-glucan to address COVID-19 due in part to variability in immune response arising from heterogeneity in polysaccharide branch and chain length for different sources and the absence of a standardized extraction method. To confirm the promising outcomes and hypotheses for bioactive compounds, more randomized and controlled clinical studies are needed. The results of such studies would have a profound effect on the prospects of food supplements and nutraceuticals as potential prophylaxis against COVID-19 and serve to help consumers to protect themselves during the post-lockdown recovery era

Postpartum human breast milk levels of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9)/NGAL complex in normal and pregnancies complicated with insulin-dependent gestational diabetes mellitus. A prospective pilot case-control study

Neutrophil gelatinase-associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) are present in a variety of human tissues and extracellular fluids. The aim of this pilot prospective case-control study was to detect NGAL and MMP-9/NGAL complex in human breast milk postpartum in women with normal and pregnancies that developed insulin-depended gestational diabetes mellitus (iGDM). We detected both biomarkers in human breast milk and concentrations were determined at the first day of colostrum secretion and two days after, in 22 normal pregnancies and 13 pregnancies with iGDM. Mean NGAL concentration decreased significantly from the first to the second sample, in both groups. Mean MMP-9/NGAL complex concentration decreased also significantly from the first to the second sample in normal pregnancies. Mean complex concentration was significantly higher in diabetic pregnancies compared to normal ones in the second sample.IMPACT STATEMENT What is already known on this subject? There is limited information on the presence of Neutrophil gelatinase-associated lipocalin (NGAL) in human milk and its physiological role. What the results of this study add? It is the first time that MMP-9/NGAL complex is detected in human milk in both normal and pregnancies complicated with insulin-depended gestational diabetes mellitus (iGDM). We confirm the presence of NGAL in colostrum of normal pregnancies and for the first time we detected NGAL in milk of pregnancies with iGDM. Concentrations of NGAL and MMP-9/NGAL complex tend to lessen postpartum in both groups. Pregnancies with iGDM compared to normal ones showed significantly higher concentration of MMP-9/NGAL complex two days after the beginning of lactation. What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to determine the levels of NGAL and MMP-9/NGAL complex in human milk postpartum in normal and pathological pregnancies. Taking into consideration the well-established NGAL’s ability to act as a bacteriostatic agent and its mucosal healing activity in gastrointestinal track, early breastfeeding of neonates is a logical recommendation. Finally, new studies on the actual physiological role of milk NGAL in neonates are necessary

Classification and discrimination of soybean (Glycine max (L.) Merr.) genotypes based on their isoflavone content

Isoflavones are phytoestrogens with various types of biological activity. Soybean (Glycine max (L.) Merr.) is the most abundant source of isoflavones in human nutrition. The present study aims to classify the different soybean genotypes according to their isoflavone contents. HPLC analysis of isoflavone content in 22 soybean genotypes was performed. The average content of individual isoflavones in the genotypes analyzed ranged from 2.8 mu g/g to 1069,9 mu g/g while the most abundant component among the 22 genotypes was malonyl-genistin. The majority of isoflavones had a significantly higher concentration (p lt 0.05) in the hybrid genotypes compared to parental genotypes implying heterosis. The principal component analysis (PCA) on isoflavone content and composition, including results in 83 genotypes, was conducted. The contents of daidzein and genistein were positively correlated, which could be explained by their biosynthetic pathways. Using the PCA, analyzed genotypes divided into six coherent groups regarding their specific isoflavone content. Malonyl-genistin and malonyl-daidzin were the most abundant components. Moreover, the significance of the cultivation year on the isoflavone content in soybean was pointed out. The overall results suggested the possibility of selection of suitable soybean extracts according to the content of malonyl-genistin